A goal for biochemists has long been to understand the way that the three-dimensional folding of proteins is encoded in their amino acid sequences. This aim is especially important for biomedical science as a field, owing to the recent explosion in information about gene, hence amino acid, sequences without a concomitant increase in information about the three-dimensional structures of proteins. Preliminary work has been performed on a new algorithm for prediction of protein folding. In the method, short segments of polypeptide, from a protein for which the primary sequence but not the three-dimensional structure is known, are compared to a library of known structures. The basis of comparison is the probability with which residues in the unknown segment might substitute through evolution for residues in segments of known structure. In test cases, segments from known structures that are similar in sequence to those from a protein treated as unknown are often found to be similar in three-dimensional structure to the true structure of the "unknown" segment. This provides a basis for reasonably reliable prediction of the torsion-angle configuration of residues in a protein. The long-term objective of this work is to produce a structure-prediction method that is sufficiently accurate that it can serve as an adequate starting point for three-dimensional model refinement procedures that would produce an accurate representation of an unknown molecule. Short-term aims are to refine and improve the method described. Specific improvements are: to produce for each residue an estimate of the reliability of the prediction of its configuration, to examine ways to improve the data base used for comparison, to include substantial information about the likely configurations to be adopted by each residue type, and to devise a means to make use of independent information about secondary structure, such as the results of circular dichroic spectroscopy.